Abundant evidence has accumulated indicating that certain forms of deafness may have an immunologic basis. This can occur as a part of the normal host defense against pathogens (i.e. viruses, bacteria) or as a consequence of an autoimmune condition which develops and has the inner ear as one of its targets. This is an important concept to understand and recognize since deafness due to immunologic events can be potentially reversed with appropriate therapy or manipulation of a host's immune response. Since McCabe's original descriptio of this new clinical entity (Autoimmune Inner Ear Disease) in 1979, many patients have been putatively identified and treated for this condition, both of which may have serious potential side effects. Often the basis of their diagnosis is the presence of rapidly progressive deafness and several tests which either point to the coexistence of systemic rheumatologic illnesses or possibly an ear-specific autoimmune condition. As in other rheumatologic conditions, autoimmune inner ear disease appears to afflict women preferentially (63%). Despite considerable interest in the disease and continued efforts in treatment, there is a compelling need for the development of a specific diagnostic test for this condition and to better understand the mechanisms at play in immunological disorders affecting the inner ear. A major drawback to accomplishing this has been lack of identification of the antigenic target(s) of AIED. Our laboratory has been integrally involved in providing the scientific basis for the original concept that the inner ear can be the target of the immunological responses and in research to determine the antigenic target of this disorder, in the hopes of developing a sensitive and specific means of diagnosing afflicted patients. The specific aims are to identify inner ear antigens associated with AIED, to determine the functional targets of autoimmunity in AIED and to investigate the immunological mechanisms of inner ear inflammation that are etiopathogenic in AIED. We believe that the progress that has been made in this field is such that significant breakthroughs in both diagnosis and treatment are readily achievable in the near future.